A new mechanism of PLA-MPs inducing fatty liver formation in carp

Abstract Plastics are indispensable materials in modern industry and daily life, but they are difficult to degrade and generate microplactics (MPs). Polylactic acid microplastics (PLA-MPs) is a highly promising type of biodegradable MPs, but it also poses environmental pollution issues. As a central organ for detoxification, the liver is also an important target organ for MPs exposure. However, the effects of PLA-MPs on the liver health of animal-derived food species such as common carp ( Cyprinus carpio L.) and the underlying molecular mechanisms of PLA-MPs remain unclear. To investigate the hepatotoxic mechanisms in carp, we established a PLA-MPs exposure model. Transcriptomic analysis revealed 4276 up-regulated and 4073 down-regulated genes. Ferroptosis and lysosomes are two Kyoto Encyclopedia of Genes and Genomes pathways both enriched for differentially expressed genes. Exposure to PLA-MPs led to excessive accumulation of reactive oxygen species, Fe 2+ , and lipid peroxidation, induced lysosomal homeostasis imbalance and triggered features characteristic of ferroptosis in carp liver, and led to the formation of fatty liver. Our results indicated that PLA-MPs contamination can impair hepatic health in carp, with lysosomal homeostasis imbalance plays a potential role in oxidative stress-mediated hepatic ferroptosis. This study provides scientific support for sustainable aquaculture, food safety and the "One Health" concept.